Targeting the delivery of toxins to malignant cells by complexing the toxin to monoclonal antibodies which recognize the cancer cells is becoming an effective approach to cancer therapy. The toxin-monoclonal antibody conjugates preferentially bind to and selectively kill the cancer cells [D. A. Vallera et al., Science 222: 512 (1983); E. S. Vietetta et al., Science 238: 1098 (1987)].
The trichothecenes are a family of toxic fungal secondary metabolites which posses a characteristic 12,13-epoxy-trichothecene nucleus. The subsequent addition of several different oxygen-containing substituents to this nucleus leads to the production of over 60 different trichothecenes [C. Tamm and W. Breitenstein, In "The Biosynthesis of Mycotoxins," (Steyn, P. S., ed.), pp. 69-101, Academic Press, New York (1980)].
As a group, the trichothecenes appear to be promising toxins for the production of immunotoxins. The molecules are relatively small in size, and the class includes members with a wide range of toxic properties. Trichothecenes are potent inhibitors of protein synthesis [C. J. Carter and M. Cannon, Biochem. J. 166: 399-409 (1977); see also: Protection Against Trichothecene Mycotoxins, Natural Academy Press, Washington, DC, pp. 129-138 (1983)]. This diversity provides the potential to design anticancer agents to meet specific requirements. There is a medically important need for a variety of trichothecenes.
Prior to this time the trichothecenes neosolaniol, 8-propionylneosolaniol, and 8-isobutyryl-neosolaniol were available in relatively small amounts as minor components of fermentation broths [see M. N. Beremand, Abstracts of Yeast Genetics and Molecular Biology, p. 93 (1986); W. W. A. Bergers et al., Appl. Environ. Microbiol. 50: 656-662 (1985); A. Visconti et al., J. Assoc. Off. Anal. Chem. 70: 193-196 (1987)]. Structures of these materials are shown below.
______________________________________ ##STR1## Trichothecene R ______________________________________ Diacetoxyscirpenol (DES) H Neosolaniol [Compound (1), Neo] OH 8-Propionyl-neosolaniol OCOCH.sub.2 CH.sub.3 [Compound (2), P-Neo] 8-Isobutyryl-neosolaniol OCOCH(CH.sub.3).sub.2 [Compound (3), B-Neo] T-2 toxin OCOCH.sub.2 CH(CH.sub.3).sub.2 ______________________________________